Key PointsQuestion
What is the risk of exposure to alcohol-based disinfectants (ABDs), frequently used for infection control, in premature infants in neonatal incubators?
Findings
In this quality improvement study including 28 premature infants in neonatal incubators, alcohol was continuously detected from all 68 blood samples obtained; its concentration was primarily associated with evaporated alcohol from ABDs inside the neonatal incubator. A simple method to reduce alcohol evaporation from ABDs was associated with decreasing the alcohol concentration inside the neonatal incubators and in premature infants.
Meaning
The findings of this study suggest that infants in incubators systemically absorb evaporated alcohol from ABDs and that reducing their exposure may be easily achieved.
Importance
The risk of premature infants in neonatal incubators exposed to evaporated alcohol from alcohol-based disinfectants (ABDs) is unknown.
Objective
To assess alcohol concentrations in the peripheral blood of premature infants and neonatal incubators.
Design, Setting, and Participants
A quality improvement study comparing 2 different populations before and after introduction of ABD practice (ABD-PRAC) was conducted in a neonatal intensive care unit of a single tertiary hospital in Japan. Participants included premature infants who were born before 34 weeks of gestational age and received medical care in neonatal incubators. The study consisted of 3 periods: (1) September 1, 2020, to August 1, 2021 (prospective observation of pre–ABD-PRAC, (2) August 2 to August 22, 2021 (introduction of ABD-PRAC to medical staff and parents in the neonatal intensive care unit), and (3) August 23, 2021, to March 31, 2022 (prospective observation of post–ABD-PRAC). No follow-up studies were initiated.
Interventions
An ABD-PRAC that aimed to reduce alcohol evaporation from ABDs inside neonatal incubators was instituted: (1) place alcohol preps in the incubator just before use and remove them from the incubator as soon as possible and (2) withhold placing hands into the incubators until 60 seconds after using ABDs for disinfection (applied only to family members).
Main Outcomes and Measures
Blood alcohol concentration and evaporated alcohol concentrations in neonatal incubators.
Results
Disinfectant practice was assessed among 28 infants during the pre–ABD-PRAC (17 infants [10 girls]; median gestational age at birth, 29.4 [IQR, 26.3-30.3] weeks) and post–ABD-PRAC (11 infants [3 girls]; median gestational age at birth, 30.0 [IQR, 25.3-32.2] weeks) study periods. The median blood alcohol concentration was 7.0 (IQR, 5.4-9.3) mg/dL pre–ABD-PRAC and 4.2 (IQR, 2.5-7.2) mg/dL post–ABD-PRAC. The median evaporated alcohol concentration inside neonatal incubators during pre–ABD-PRAC during the day was 23.6 (IQR, 15.9-36.5) ppm and, at night, was 13.2 (IQR, 8.9-19.4) ppm; during post–ABD-PRAC, the concentration was 9.4 (IQR, 6.0-16.0) ppm during the day and 5.7 (IQR, 3.6-9.7) ppm at night. The introduction of ABD-PRAC at 22 weeks’ corrected gestational age was associated with a lower blood alcohol concentration in premature infants: regression coefficient value, −8.3 (95% CI, −12.0 to −4.7).
Conclusions and Relevance
In this study, alcohol evaporated from ABDs was absorbed by premature infants in neonatal incubators. The findings suggest that introduction of ABD-PRAC was associated with lower alcohol concentrations in neonatal incubators and in the blood of premature infants.
Alcohol-based disinfectants (ABDs), which include alcohol hand sanitizers and ABD prep pads (alcohol preps), are commonly used as antiseptics in neonatal intensive care units (NICUs).1 The importance of their use for infection control in NICUs has gained increasing attention over the years because premature infants are immunocompromised and are highly vulnerable to microorganisms.2-5 Furthermore, alcohol can cause irreversible brain damage to fetuses, which is known as fetal alcohol spectrum disorders.6-8
Neonatal incubators, which accommodate infants in warm and humid conditions, play an important role in protecting infants from the invasion of pathogens by providing clean air and have contributed to lowering premature infant mortality.9 In contrast, such confined spaces may have a detrimental effect on infants if there is a noxious volatile organic compound.10 To our knowledge, the level of alcohol exposure in infants in incubators has not been investigated.
To examine whether alcohol evaporated from ABDs inside neonatal incubators is systemically absorbed by premature infants, we measured the blood alcohol concentration (BAC) in premature infants and in the air of neonatal incubators. We then conducted a study by introducing a newly designed ABD practice (ABD-PRAC) and evaluated its association with reducing alcohol exposure in premature infants.
Study Design and Participants
A quality improvement study that followed the Standards for Quality Improvement Reporting Excellence (SQUIRE) reporting guideline was conducted in a level 3 NICU with 27 beds in Tsukuba University Hospital (Ibaraki, Japan) from September 1, 2020, to March 31, 2022. Infants were included only if they were born at Tsukuba University Hospital before 34 weeks of gestational age and their care was managed inside neonatal incubators. Two types of neonatal incubators (Incu i and V-2100G; Atom Medical Corp) were used. Written informed consent was obtained from the parents of all recruited infants. Infants with life-threatening general conditions and congenital malformations and those born when volatile organic compound sensors were unavailable were excluded. This study was approved by the ethics committee of Tsukuba University Hospital and other participating institutions.
The study consisted of 3 periods. The first period (September 1, 2020, to August 1, 2021) was the prospective observational study held to survey the baseline of alcohol concentrations in the infants’ blood and in the air of neonatal incubators (pre–ABD-PRAC introduction). In the second period (August 2 to August 22, 2021), we designated 3 weeks to introduce the ABD-PRAC to medical staff and parents in the NICU. In the third period (August 23, 2021, to March 31, 2022), a prospective observational study was held to survey the change of alcohol concentration in the infants’ blood and in the air of neonatal incubators after the introduction of ABD-PRAC in the NICU (post–ABD-PRAC introduction). No samples were obtained during the ABD-PRAC introduction phase, and no individual patient overlapped between the pre–ABD-PRAC and post–ABD-PRAC introduction periods. No follow-up studies were initiated.
Peripheral Blood Collection
Blood samples for alcohol analysis were additionally collected during routine clinical blood sampling (eMethods 1 in Supplement 1). Contamination and evaporation of alcohol from the samples were prevented as much as possible. Samples from infants who received alcohol excipient–containing medications were excluded.
Analysis of Alcohol Concentrations
Static headspace gas chromatography–coupled mass spectrometry was used to analyze alcohol in small volumes of peripheral blood (eMethods 2, eTable 4, eTable 5 in Supplement 1). We adopted real-time volatile organic compound sensors specialized for detecting ethanol (COD-203, New Cosmos Electric Co Ltd) (eMethods 3 in Supplement 1). The following alcohol disinfectants are used in our NICU: alcohol preps containing ethanol, 76.9% to 81.4% (vol/vol), and alcohol hand sanitizers containing ethanol, 83% (vol/vol), with chlorhexidine, 0.2%.
The ABD-PRAC was designed to reduce the evaporation of alcohol from ABDs inside the incubators without influencing infection control in the NICU. The ABD-PRAC consisted of the following: (1) place alcohol preps in the incubator just before use and remove them from the incubator as soon as possible and (2) withhold placing hands into the incubators until 60 seconds after using ABDs for disinfection (applied only to family members). The NICU health care professionals were blinded to alcohol concentration levels in the incubators and in the blood of premature infants throughout the study period. To investigate the association between ABD-PRAC and infection control, culture-proven sepsis and the amount of alcohol preps used were recorded.
Blood alcohol concentrations were analyzed using linear mixed-effects models. Fixed effects were selected based on the independent variables according to the importance of the absorbing site of alcohol (eg, airway and skin) and the nature of alcohol exposure in infants (eg, indirectly with evaporated alcohol or directly with alcohol preps): corrected gestational age (CGA), ABD-PRAC, respiratory support, arterial catheterization, and the interaction between CGA and ABD-PRAC. Intercept and CGA were used as random effects. ABD-PRAC was time-invariant, while the other variables were time-varying. Twenty-two was subtracted from the CGA to use week 22 as the origin. The interaction term CGA × ABD-PRAC was included since alcohol absorption would change per the CGA and may interfere with ABD-PRAC measurement; the need for frequent and intensive medical care using ABDs generally decreases by infantile maturation. Time-weighted average alcohol concentrations in the incubator during day (6:00 am-6:00 pm) and night (6:00 pm-6:00 am), total time during which alcohol concentrations exceeded 15 ppm, range of the highest and lowest concentrations, and coefficient of variation of concentrations were analyzed using a linear regression model after log-transformation. Explanatory variables were the same as the above fixed effects. Standardized regression coefficients were also calculated where explanatory variables were standardized and response variables were not. A 2-sided P value <.05 was considered statistically significant. Statistical analyses were performed using Stata, version 14.0 (StataCorp LLC) and SAS, version 9.4 (SAS Institute Inc).
Patient and sample characteristics are reported in Table 1. Twenty-eight premature infants were enrolled in this study (pre–ABD-PRAC, 17 [10 girls]; median gestational age at birth, 29.4 [IQR, 26.3-30.3] weeks; and post–ABD-PRAC, 11 [3 girls]; median gestational age at birth, 30.0 [IQR, 25.3-32.2] weeks). The overall median gestational age of the infants was 29.6 (IQR, 25.5-31.0 weeks) and the median birth weight was 1244 (IQR, 743-1413) g.
Alcohol was detected in all blood samples obtained from premature infants in the incubators (ethanol was the only alcohol detected on gas chromatography–coupled mass spectrometry analysis). Median BAC of infants in incubators was 7.0 (IQR, 5.4-9.3) mg/dL in 41 samples analyzed from 17 infants, which was higher than that of control cord blood samples exposed to NICU air (0.2 [IQR, 0.1-0.4] mg/dL; 3 samples from 3 infants) or to 100-ppm alcohol-containing air (0.5 [IQR, 0.3-0.8] mg/dL; 3 samples from 3 infants) (Figure 1A). Alcohol was continuously detected from individual infants at different CGAs (39 samples analyzed from 15 infants; Figure 1B and Table 1). The kinetics of alcohol concentrations in incubators revealed dynamic changes with multiple increases reaching high levels (Figure 1C; eFigure 1 in Supplement 1). The median alcohol concentration in incubators during the day (23.6 [IQR, 15.9-36.5] ppm) was higher than that during the night (13.2 [IQR, 8.9-19.4] ppm) (Figure 1D).
Alcohol concentration increases greater than 30 ppm were analyzed using the video recording data retrospectively (eMethods 4 in Supplement 1). Alcohol concentration increases were exclusively associated with medical care routines in incubators that were classified into 3 types according to the use of ABDs and median alcohol concentration in incubators as follows: medical care by staff using alcohol preps in incubators (77.2 [IQR, 50.4-117.4] ppm; n = 332), medical care by staff without using alcohol preps in incubators (37.1 [IQR, 32.7-46.2] ppm; n = 442), and skin-to-skin contact of family members, who performed hand disinfection using ABDs before contact with infants (58.9 [IQR, 41.1-85.5] ppm; n = 9) (eFigure 2 in Supplement 1). In experimental settings, lower evaporated alcohol concentration was associated with reduced time of alcohol prep kept inside incubators (eFigure 3A in Supplement 1). After disinfecting hands with ABDs, a lower evaporated alcohol concentration inside incubators was associated with sufficient drying time (eFigure 3B in Supplement 1) or by wearing medical gloves, which was associated with reduced alcohol concentration regardless of the drying time (eFigure 3C in Supplement 1). From these observations, we established ABD-PRAC to reduce the evaporation of alcohol in incubators.
After introduction of ABD-PRAC, the median BAC in premature infants decreased to 4.2 (IQR, 2.5-7.2) mg/dL in 27 samples analyzed from 11 infants (Figure 1A). Alcohol was still continuously detected in infants at different CGAs (25 samples analyzed from 9 infants) (Figure 1B). Kinetics of weekly and daily evaporated alcohol concentrations in incubators showed a decrease in peak values of individual increases and in time-weighted average values (Figure 1C; eFigure 1 in Supplement 1). Median alcohol concentration in incubators (a total of 378 days were analyzed) during the day was 9.4 (IQR, 6.0-16.0) ppm and during the night was 5.7 (IQR, 3.6-9.7) ppm (Figure 1D). The incidence of sepsis among infants and the monthly amount of alcohol prep use did not change substantially from pre- to post–ABD-PRAC introduction (Table 1; eFigure 4 in Supplement 1).
Linear mixed-effect model analysis (Table 2; eTable 1 in Supplement 1) showed that the explanatory variables most associated with decreased BAC, reported using regression coefficients, were introduction of ABD-PRAC at 22 weeks’ CGA (−8.3; 95% CI, −12.0 to −4.7), followed by mechanical ventilation (−4.8; 95% CI, −7.3 to −2.3), nasal continuous positive airway pressure (−3.3; 95% CI, −5.6 to −1.1), and CGA (−0.7; 95% CI, −1.2 to −0.3). An association was noted with CGA × ABD-PRAC for BAC (0.8; 95% CI, 0.2-1.3) but not the blood sampling route (−1.7; 95% CI, −3.9 to 0.5).
The association of 4 evaporated alcohol concentration measurements in incubators (ie, time-weighted average, total time of exposure to ≥15 ppm of alcohol, coefficient of variation, and range) with explanatory variables was analyzed. The ABD-PRAC was associated with a decrease in all measurements of evaporated alcohol concentration (Table 2; eTables 1, 2, and 3 in Supplement 1). An association was noted between CGA and decreased evaporated alcohol concentration range and coefficient of variation (Table 2; eTables 1, 2, and 3 in Supplement 1), and CGA × ABD-PRAC was associated with all measurements of evaporated alcohol concentration (Table 2; eTables 1, 2, and 3 in Supplement 1).
The kinetics of BAC during pre–ABD-PRAC were the highest in early CGAs, which gradually decreased toward later CGAs, although the concentration at post–ABD-PRAC remained constant at a lower level (Figure 2A). The kinetics of the evaporated alcohol concentration of time-weighted average and total time of exposure to 15 ppm or more of alcohol showed constant levels irrespective of the CGA, which was apparently lower in post–ABD-PRAC than in pre–ABD-PRAC (Figure 2B; eFigure 5B, eFigure 6A and B in Supplement 1). Coefficient of variation and range of evaporated alcohol concentration pre–ABD-PRAC were the highest in early CGAs, which gradually decreased toward later CGAs, although post–ABD-PRAC results remained constant at a lower level (Figure 2C; eFigure 5A, eFigure 6C and D in Supplement 1).
To our knowledge, this is the first study to examine neonatal alcohol exposure combined with BAC. Premature infants were exposed to alcohol evaporated from ABDs, and the alcohol was absorbed systemically via the airway and skin throughout the period of incubator management. The introduction of ABD-PRAC was associated with reduced alcohol concentration in neonatal incubators and BAC in premature infants.
In this study, we found sustained exposure of premature infants within incubators to alcohol. Perinatal alcohol exposure is hazardous and can affect the developing neurons by altering mitochondrial function,11 inducing apoptosis,12 inhibiting neurotransmitter N-methyl-d-aspartate receptors,13 and inhibiting migration,14,15 causing permanent neurodevelopmental abnormalities (ie, fetal alcohol spectrum disorders).7,16 Incidental alcohol concentrations in newborn infants that cause severe physical symptoms or death have been reported at BACs greater than or equal to 43 mg/dL.17,18 However, these studies observed the toxic effects caused by a single or intermittent high-concentration alcohol exposure. Therefore, the risk of intoxication cannot be applied to cases of sustained low-concentration exposure found in infants in incubators. Considering a BAC of 43 mg/dL17,18 as a lowest observed adverse effect level of acute alcohol exposure in infants, the lowest observed adverse effect level of chronic alcohol exposure in infants can be estimated by applying the uncertainty factor of 10 (ie, 4.3 mg/dL).19 In our study, the median BAC pre–ABD-PRAC (7.0 mg/dL) exceeded this value, while the median BAC post–ABD-PRAC was below this value (4.2 mg/dL) (Figure 1A). To ensure the safety of infants, no observed adverse effect level for sustained exposure to alcohol in premature infants should be established and used to assess risk, and BACs should be maintained at the lowest possible levels. In this study, we focused on ethanol, but another type of alcohol, isopropanol, commonly used in ABDs,20-22 shares strong structural and chemical similarity with ethanol23,24 and may need to be considered similarly.
The aim of ABD-PRAC was to decrease evaporated alcohol from ABDs inside neonatal incubators. The volatile organic compound sensors set inside the incubators provided real-time, accurate data regarding the overall exposure of premature infants to alcohol. Although these sensors can detect volatile organic compounds other than alcohol, they were sufficient to identify the cause of alcohol increase and evaluate its association with ABD-PRAC. Increased alcohol concentration in incubators due to evaporated alcohol from ABDs was only reported in experimental settings.10 Combined with video monitoring, we found that the periods of high alcohol levels in incubators were closely related to the medical procedures that required the use of ABDs. We also found that, in addition to sufficient drying time, wearing medical gloves after applying ABDs to the hands could prevent the evaporation of alcohol inside the incubator to an extent, regardless of the drying time. These findings are possibly useful for the management of infants in NICUs where emergent intervention is frequent.25 Reducing the duration of alcohol preps inside the incubator was also associated with lower alcohol evaporation, which was not associated with infection control in the NICU.
To further decrease the BAC in premature infants, we evaluated the factors that affected the absorption of alcohol. Penetration of alcohol through immature skin is considered the key factor for systemic absorption of alcohol.26 The ABD-PRAC and ventilatory support were associated with lower BACs (Table 2), indicating that, in addition to skin, airway is a key factor for alcohol absorption in premature infants in incubators. An interaction between CGA and ABD-PRAC was detected for BACs (Table 2), which was observed as a gradual decrease in BAC by CGA in pre–ABD-PRAC and as a low concentration in post–ABD-PRAC (Figure 2A). A gradual decrease in alcohol concentration pre–ABD-PRAC may be explained as maturation of skin with increasing CGA, which decreased alcohol penetration.27 However, alcohol was also detected in post–ABD-PRAC samples of infants with early CGAs, who similarly received mechanical ventilation or arterial catheterization (Figure 1B), and BAC did not decrease with increasing CGA. This suggests that factors other than skin barrier maturation,27 kidney excretion capability,28,29 and metabolic enzyme activity30 (which develops after birth regardless of postconceptional age) affect the absorption of alcohol. Analysis of alcohol concentration in neonatal incubators revealed a similar pattern pre- and post–ABD-PRAC in coefficient of variation and range to that of BAC, but not in time-weighted average or total time exposure to greater than or equal to 15 ppm of alcohol (Figure 2; eFigure 5 in Supplement 1). Coefficient of variation and range of results may be influenced by a frequent and rapid increase in alcohol concentration due to alcohol evaporation from medical care that requires the use of ABDs that gradually decreased in the later CGAs owing to the reduction in the need of frequent and intensive medical care, indicating infantile maturation. However, these results decreased even in early CGA post–ABD-PRAC (Figure 2; eFigure 5 in Supplement 1). The chemical properties of alcohol, including low boiling temperature and high water solubility,24 may have facilitated its rapid evaporation and immediate absorption through the premature skin, indicating that maturation of premature infants during neonatal incubation may not be sufficient to suppress the absorption of alcohol. Blood sampling method did not influence BACs of premature infants in incubators (Table 2; eTable 1 in Supplement 1), which may support the importance of the evaporated alcohol for absorption rather than liquid alcohol contained in alcohol preps that come into direct contact with the skin. Therefore, to decrease BACs, reducing the evaporated alcohol from ABDs in neonatal incubators may be the best approach.
Alcohol, chlorhexidine, and povidone-iodine are commonly used skin disinfectants for premature infants.20,31-34 They have broad antimicrobial activity but can be systemically absorbed through immature skin,35-39 which is of great concern in neonatal care.33-35,39-41 Acute cytotoxic effects, such as skin inflammation35,42-47 and hypothyroidism,48,49 has been reported; however, long-term effects in infants are unknown.36,41 In infants, the neurotoxic effects of these disinfectants, which has been reported in clinical studies of adults and in laboratory studies, is of great concern.50-54 With the high risk of developmental problems, including cognitive, behavioral, attentional, and socialization deficits, in preterm children,3,55-60 preventing the absorption of neurotoxic agents with interventions, such as our ABD-PRAC, seems necessary. Compared with alcohol, chlorhexidine stays longer on the skin, induces longer duration of antimicrobial activity,61 and induces gradual absorption that cannot be washed off,62 reaching its peak blood concentration after 2 to 3 days.36 These observations may reflect the chemical properties of chlorhexidine, which has a higher boiling temperature and lower water solubility than alcohol.63 Thus, the optimal disinfectants for use in the care of premature infants should be selected based on reliable antimicrobial activity required for medical procedures, while preventing toxic effects resulting from systemic absorption and with adequate consideration of their chemical properties.
This study has limitations. First, it was not a randomized clinical trial. However, with this study, we showed alcohol absorption occurring during premature infant care, which is quite alarming. Second, it was a single institutional study using 2 types of neonatal incubators from a single manufacturer, which may not accurately represent the alcohol exposure of premature infants in other incubators. However, ABDs are used in NICUs worldwide, and increased evaporated alcohol concentrations were observed in neonatal incubators of other institutions (eFigure 7 in Supplement 1) and in other manufacturers.7 Therefore, increases in evaporated alcohol concentrations in neonatal incubators may be a universal occurrence. Third, we could not analyze maternal BACs. However, it is known that alcohol is detected at minimal levels in a small proportion of woman who are pregnant in Japan.64
In this study, alcohol evaporated from ABDs was absorbed by premature infants inside incubators. The ABD-PRAC was associated with lower BACs in infants, and is a simple and safe procedure that can be introduced in any NICU. The sustained infantile exposure to alcohol cannot be overlooked, and further studies of its toxic effects are warranted.
Accepted for Publication: January 10, 2023.
Published: February 24, 2023. doi:10.1001/jamanetworkopen.2023.0691
Correction: This article was corrected on March 21, 2023, to fix a grant number in Funding/Support.
Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License. © 2023 Hitaka D et al. JAMA Network Open.
Corresponding Authors: Shoji F. Nakayama, MD, PhD, Health and Environmental Risk Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan (fabre@nies.go.jp); Satoshi Fujiyama, MD, PhD, Department of Pediatrics, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki 305-8576, Japan (fujiyama.satoshi.cw@ms.hosp.tsukuba.ac.jp).
Author Contributions: Drs Hitaka and Fujiyama are co–first authors, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Hitaka, Fujiyama, Hamada, Miyazono, Takada.
Acquisition, analysis, or interpretation of data: Hitaka, Fujiyama, Nishihama, Ishii, Hoshino, Nakayama, Takada.
Drafting of the manuscript: Hitaka, Fujiyama, Nishihama, Ishii, Hamada, Nakayama, Takada.
Critical revision of the manuscript for important intellectual content: Fujiyama, Nishihama, Hoshino, Miyazono, Nakayama, Takada.
Statistical analysis: Hitaka, Ishii, Nakayama, Takada.
Obtained funding: Hitaka, Fujiyama.
Administrative, technical, or material support: Hitaka, Nishihama, Hamada, Nakayama, Takada.
Supervision: Hitaka, Fujiyama, Hoshino, Miyazono, Nakayama, Takada.
Conflict of Interest Disclosures: Dr Hitaka reporting holding patents for JP7162315B,JP7154519B, and JP7188720B, and patents pending for JP2022083367A, JP2022083369A, JP2022083364A, JP2022083366A, and JP2022173640A. Dr Fujiyama reported holding patents for JP7162315B, JP7154519B, and JP7188720B, and patents pending for JP2022083367A, JP2022083369A, JP2022083364A, JP2022083366A, and JP2022173640A. Dr Ishii reported holding a patent for JP7162315B and a patent pending for JP2022083367A. No other disclosures were reported.
Funding/Support: This study was supported under collaborative research between New Cosmos Electric Co, Ltd and University of Tsukuba and by the Japan Agency for Medical Research and Development under grant JP 22ym0126803.
Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 2.
Additional Contributions: We thank Tsukuba Clinical Research and Development Organization for their support in carrying out this clinical study. Hirokazu Akahoshi (Tsukuba University Hospital) provided support in collecting data and helping with the experiments. Chieko Hirosawa and Yuka Yoshikawa provided secretarial assistance and Mayumi Honda and Ikuko Nakamura, PhD, provided technical assistance. No financial compensation was provided.
Additional Information: New Cosmos Electric Co Ltd provided the volatile organic compound sensors and extracted the data from volatile organic compound sensors.
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